Nonalcoholic steatohepatitis (NASH) is an important and increasing contributor to liver cancer (LC). We aimed to investigate the mortality trends of liver cancer due to NASH (LCN) over the past several decades and projected to 2050 and evaluated the behavioral factor and metabolic risk factor related LCN mortality, analyzing health inequality, and providing forward-looking insights to guide global health interventions and policy formulation.

The Bayesian spatio-temporal model was employed to evaluate the temporal and spatial trends of age-standardized mortality rates (ASMRs) for LC due to NASH (LCN). The Bayesian Age-Period-Cohort model was used to predict ASMR and mortality in 2022–2050. Temporal trends were analyzed by calculating the average annual percent change (AAPC) of ASMRs. Heath inequalities, frontier analysis, and decomposition analysis were applied to clarify the issues.

From 1990 to 2021, the ASMR of LCN showed an upward trend worldwide (AAPC = 0.82). The Americas had the fastest growth in ASMR for LCN (AAPC = 2.03), whereas the African region had the highest ASMR of LCN. With the exception of the Western Pacific region, which had a stable trend (AAPC = –0.1, 95% confidence interval: –0.48 to 0.28), the ASMRs in the other five WHO regions presented an upward trend. The LCN ASMR was consistently highest in low-income areas and lowest in high-income areas. Areas with a low sociodemographic index quintile or minimal health system always had the highest ASMR of LCN. The ASMR of LCN in China and India are predicted to increase more remarkably after 2022. Health inequity persists worldwide, and countries with a low development level bear a greater burden of LCN mortality. Decomposition analysis showed that the increase in LCN mortality was mainly attributable to epidemiological changes and age structure. The mortality burden of smoking and high fasting plasma glucose (HFPG)-related LCN has continued to rise over the last three decades.

This study shows the growing contribution and significant health inequality of LCN mortality at global, regional, and national levels, highlighting the need for targeted public health strategies in special regions such as the Americas and Africa.